儿童急性淋巴细胞白血病患者接种流感疫苗的有效性和安全性系统评价

Evaluation of Effectiveness and Safety of Influenza Vaccine in Children with Acute Lymphoblastic Leukemia: A Systematic Review

目的通过检索已出版的文献,回顾有关儿童急性淋巴细胞白血病(ALL)患者接种流感疫苗有效性和安全性,探索最优的接种策略,为临床提供参考。方法按照PICOS原则制定研究主题的检索策略,检索Pub Med、Em Base等英文文献数据库,由两位研究者独立使用PRISMA流程图筛选符合标准的文献,提取研究数据并进行评价。结果共检索到文献186篇,经筛选获有效文献29篇。评价研究文献显示,多数ALL患儿接种灭活流感疫苗可产生中等强度的免疫应答,各亚型/系的血清抗体保护率可分别达到33%~85%(A/HIN1)、38%~92%(A/H3N2)、14%~92%(B)及37%~88%(pH1N1);血清阳转率可分别达到0%~65%(A/HIN1)、20%~85%(A/H3N2)、0%~92%(B)及11%~81%(pH1N1),低于健康儿童或实体肿瘤患儿。疫苗预防实验室确诊的流感或流感样病例的临床使用有效性的研究有限,研究结果有争议。接种时有较高的基线淋巴细胞计数、Ig G水平、结束化疗或低化疗强度阶段、高年龄段患儿以及给予加强剂次可能会有较强的免疫应答;减活流感疫苗、高剂量流感疫苗、含佐剂流感疫苗均不能改善ALL患儿的免疫应答。疫苗在各治疗阶段接种均有较好的耐受性,不良反应轻微。结论 ALL患儿接种流感疫苗安全性好,可产生中等强度的血清学保护作用,建议维持治疗阶段接种标准剂量灭活流感疫苗;疫苗的临床有效性还有待设计良好的临床试验验证。

OBJECTIVE The effictiveness and safety of influenza vaccine for children with acute lymphoblastic leukemia(ALL)were reviewed by searching the published literature to explore the optimal vaccination strategy for clinical reference.METHODS According to the principles of PICOS,the retrieval strategy of the research topic was developed,and the english literature databases such as Pub Med and Embase were searched.RESULTS A total of 186 literatures were retrieved,29 of which were valid.Studies have shown that inactivated influenza vaccination in most children with ALL can produce a moderate intensity immune response,and the seroprotection rates of subtypes/lines can reach 33%-85%(A/HIN1),38%-92%(A/H3N2),14%-92%(B) and 37%-88%(pH1 N1),respectively.Seroconversion rates were 0%-65%(A/HIN1),20%-85%(A/H3 N2),0%-92%(B) and11%-81%(pH1N1),respectively,which were lower than those of healthy children or children with solid tumors.Studies on the effectiveness of vaccines in preventing laboratory-confirmed influenza or influenza-like illness are limited and the results are conflicting.Higher baseline absolute lymphocyte counts,Ig G levels at the time of vaccination,off or low-intensity stages of chemotherapy,older children,and booster doses may result in a stronger immune response.Live attenuated influenza vaccine,high-dose influenza vaccine and adjuvant influenza vaccine did not improve the immune response of children with ALL.The vaccine was well tolerated in all treatment stages with mild adverse reactions.CONCLUSION Available data suggest that the standard dose of inactivated influenza vaccine should be administered at the maintenance chemotherapy stage.The vaccine’s clinical effectiveness has yet to be verified in welldesigned clinical trials.